Clinical and laboratory procedures in chemistry and biotechnology frequently rely on the separation of individual species from mixtures of similar species in liquid solutions. Various different types of chromatography, particularly in the high performance mode, are effective and useful methods of accomplishing these separations. Despite the high level to which these techniques have been developed, however, they remain limited to specific types of interactions or by the degree or extent to which species can be separated on the basis of differences in migration rates. There is no known method by which a universal separation medium can be adapted, treated, formed or otherwise tailored to isolate any one selected species from an unlimited variety to the exclusion of all others.
Mosbach and coworkers, as exemplified by U.S. Pat. No. 5,110,833 and 5,461,175, have developed what they call "imolecular imprinting," which is a method of preparing polymers by polymerizing monomers around "print molecules." Once polymerization is complete, the print molecules are removed, leaving imprints of the print molecules in the polymer. The imprinted polymer then serves as a template to selectively adsorb the same print molecules when subsequently applied, or other molecules or molecular combinations with similar recognition parameters. Mosbach et al. claim that these imprinted polymers can serve the same functions as enzymes, antibodies or chromatographic media.
The monomers are characterized by Mosbach et al. as functional monomers since they bear charged or otherwise functionalized atoms or groups. The resulting polymers are therefore similarly charged or functionalized. The print molecules selected for use are also charged or functionalized in a manner complementary to the functional monomers. The result is a complexation between the polymer and the print molecules. The template retention effect referred to in the preceding paragraph is thus accompanied by, and is in fact secondary to, this smaller scale, molecular-type complexation between the print molecules and individual monomers or their ligand residues.
The work of Mosbach et al. suggests that the molecular imprints left by the print molecules serve only to help retain further such molecules subsequently passed through the gel after these molecules have been drawn into position by the smaller-scale complexation with the ligand or ligands in the imprinting sites. A further suggestion from this work is that to achieve a polymer bearing a molecular imprint one must first form a complex between the print molecule and the monomer. Both suggestions tend to limit the application of "molecular imprinting" as it is currently known to polymers that are not inert, and likewise to print molecules that are not inert, i.e., to monomers and print molecules that form complexes both before polymerization and in the polymer itself.
Another drawback of the use of a functional monomer is that most of the functional monomers, if not all, will be randomly distributed in the polymer gel, and a significant proportion of the functional sites will be at locations other than those where a complex with the print molecule resided during the polymerization to form the gel. Because of these additional functional sites, the gel will exhibit very little specificity, particularly for macromolecules such as proteins which have many adsorption sites that permit attachment of the molecule to the gel in more than one mode. This leads to non-specific adsorption, and the charge on the functional monomers will thus cause the polymer gel to behave as an ion exchanger. For this reason, no polymer gel based on functional monomers has been shown to be highly specific for proteins.